Concurrent Papillary and Medullary Thyroid Carcinoma

Archives of Pathology & Laboratory Medicine, Feb 2005 by Nicolas, Marlo M, Neto, Antonio Galvao, Luna, Mario A

A 67-year-old man presented with a thyroid nodule and an elevated calcitonin level. He underwent subtotal thyroidectomy.

A follow-up computed tomographic scan of the neck a few weeks later showed 2 enlarged cervical and superior mediastinal lymph nodes suspicious for tumor involvement. Chest radiograph, chest computed tomographic scan, whole-body bone scan, and magnetic resonance imaging of the abdomen revealed no evidence of metastatic disease. Completion thyroidectomy and bilateral cervical lymph node dissection were subsequently performed.

A solitary focus of papillary thyroid carcinoma (PTC), 1.2 cm in diameter, in the left lobe, and multifocal medullary thyroid carcinoma (MTC) in both right and left lobes and isthmus, with the largest tumor focus measuring 0.7 cm in diameter, were identified. The histomorphology and immunoprofile of the primary PTC and MTC were typical. The fingerlike projections of the PTC were lined by cuboidal cells with overlapping grooved nuclei and often with ground-glass ("Orphan Annie" eye) appearance (Figure 1, a). The MTC component consisted of nests of predominantly round cells with ample, finely granular amphophilic cytoplasm and ovoid to round nuclei (Figure 1, b). The chromatin material was stippled, and the nucleoli were rarely prominent. Amyloid deposit was admixed with MTC tumor cells. The MTC component extended into the perithyroidal soft tissue.

Immunohistochemically, the lesional cells of the PTC were positive for thyroglobulin (Figure 1, a, inset) and negative for calcitonin, carcinoembryonic antigen, and chromogranin. The MTC cells were positive for calcitonin (Figure 1, b, inset), chromogranin, and carcinoembryonic antigen and negative for thyroglobulin.

There were multiple MTC metastases identified in cervical soft tissue and in 8 of 20 cervical and superior mediastinal lymph nodes. Two lymph nodes had both PTC and MTC metastases, and in each of these 2 lymph nodes the PTC and MTC metastases were closely associated (Figures 2 and 3). Amyloid material was also seen intermingled with metastatic MTC cells (Figure 2).

Cases of concurrent or mixed papillary and medullary thyroid carcinoma are rare.1-3 These patients may have RET proto-oncogene mutation.1 In some of these patients, the tumor spread to cervical lymph nodes and distant organs, causing death from metastatic disease.1

Concurrent PTC and MTC neoplasms appear to occur in 2 circumstances3: (1) PTC and MTC, being morphologically and immunophenotypically distinct tumors, are believed to arise from embryologically different cells, follicular cell (endodermal anlage) origin for PTC and C cell (ultimobranchial body) origin for MTC. In this setting, PTC and MTC may be regarded as collision tumors. (2) A common stem cell derivation for follicular and C cells is considered by others, resulting in a true follicular-parafollicular cell carcinoma.3

References

1. Papi G, Corrado S, Pomponi MG, Carapezzi C, Cesinaro A, LiVolsi VA. Concurrent lymph node metastases of medullary and papillary thyroid carcinoma in a case with RET oncogene germline mutation. Endocr Pathol. 2003;14:269-276.

2. Fugazzola L, Cerutti N, Mannavola D, et al. Multigenerational familial medullary thyroid cancer (FMTC): evidence for FMTC phenocopies and association with papillary thyroid cancer. Clin Endocrinol (Oxf). 2002;56:53-63.

3. Pastolero GC, Coire CI, Asa SL. Concurrent medullary and papillary carcinomas of thyroid with lymph node metastases: a collision phenomenon. Am J Surg Pathol. 1996;20:245-250.

Mario M. Nicolas, MD; Antonio Galvao Neto, MD; Mario A. Luna, MD

Accepted for publication August 31, 2004.

From the Department of Pathology, M. D. Anderson Cancer Center, Houston, Tex.

The authors have no relevant financial interest in the products or companies described in this article.

Reprints: Mario A. Luna, MD, Department of Pathology, M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Box 85, Houston, TX 77030 (e-mail: mluna@mail.mdanderson.org).